Abstract: FR-PO0221
New Insights into the Mechanism of Action of IV Iron Products: Kinetics of Macrophage Uptake and Their Intracellular Metabolic Fate
Session Information
- Anemia and Iron Metabolism
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Anemia and Iron Metabolism
- 200 Anemia and Iron Metabolism
Authors
- Alston, Amy Barton, Vifor Pharma Management AG, Glattbrugg, Zurich, Switzerland
- Ayala-Nunez, Vanesa, Empa, St Gallen, Switzerland
- Krupnik, Leonard, Empa, St Gallen, Switzerland
- Kissling, Vera Maria, Empa, St Gallen, Switzerland
- Rippl, Alexandra, Empa, St Gallen, Switzerland
- Eitner, Stephanie, Empa, St Gallen, Switzerland
- Wick, Peter, Empa, St Gallen, Switzerland
Background
Iron-carbohydrate complexes (IV iron) are nanomedicines that are widely used in treating people with iron deficiency anemia. IV iron products are distinguished by the carbohydrate moiety bound to the iron core (e.g. sucrose) and there are differences in their pharmacokinetics and biodistribution profiles. The main objective of this project was to dissect how different physicochemical characteristics of iron products affects their bioprocessing at the cellular level to gain a deeper understanding of their mechanism(s) of action.
Methods
Prior to initiating systematic studies of the response of macrophages, a comprehensive physicochemical characterization of two iron-carbohydrate complexes with different carbohydrate moieties: iron sucrose (IS), and ferric carboxymaltose (FCM) was performed. After treatment with IS and FCM in primary human macrophages total iron uptake, the labile iron pool (LIP), intracellular ferric iron, ferritin and soluble transferrin receptor production were measured to determine the rate and extent of iron nanoparticle uptake and metabolism. Additionally, innovative correlative microscopy techniques and endocytic inhibitors were used to study their mode of cellular entry.
Results
Both complexes exhibited individual, dynamic profiles of internalization and biodegradation in human macrophages. IS was observed to be rapidly internalized and processed within endolysosomes (confirmed by endocytic inhibitors) compared to FCM. This resulted in faster iron release into the LIP. Conversely, FCM is sequestered for an extended period of time in endosomes which become enlarged before biodegradation of the nanoparticle and release of iron. This leads to a slow and sustained release of iron into the LIP and a delayed production of intracellular ferritin and soluble transferrin receptor.
Conclusion
Our results illustrate that the physical characteristics of IS and FCM influence their metabolic fate. It was observed that IS undergoes rapid cellular uptake and nanoparticle degradation compared to FCM which is markedly slower and controlled. The results of these detailed in vitro studies provide unprecedented insight into the metabolic fate of IV iron products that advances understanding of their pharmacokinetic and pharmacodynamic profiles in vivo.
Funding
- Commercial Support – CSL Vifor